A MENDELIAN RANDOMIZATION STUDY OF CORONARY ARTERY DISEASE AND THREE AMINO ACIDS: ALANINE, GLYCINE, AND GLUTAMINE

Author

Allan Uribe, CUNY School of Public HealthFollow

Date of Degree

6-4-2019

Document Type

Dissertation

Degree Name

Doctor of Public Health (DPH)

Department

Epidemiology and Biostatistics

Advisor(s)

C. Mary Schooling

Committee Members

Shiro Horiuchi

Jennifer Dowd

Subject Categories

Cardiovascular Diseases | Epidemiology | Genetics | Other Public Health | Public Health

Keywords

amino acid, mendelian randomization, ischemic heart disease

Abstract

Cardiovascular disease is the leading cause of death worldwide. Coronary Artery Disease (CAD) accounts for the majority of those deaths. Observational studies have identified risk factors that have been helpful in lowering the death rate, including hypertension, high cholesterol, diabetes, smoking, physical inactivity and poor diet. The effects of these risk factors on CAD remain unclear. To clarify the effect of three amino acids, alanine, glutamine, and glycine on CAD I applied a two sample Mendelian randomization analysis to extensively genotyped observational data. In a sample with up to 184,000 individuals and approximately 60,000 controls, SNPs that reached genome wide significance with each amino acid were identified. Linkage equilibrium was assessed for each SNP. Known pleiotropy was assessed using the phenoscanner database. Unknown pleiotropy was assessed using MR-Egger. Using the IVW approach, the odds of CAD was 0.89 lower per one standard deviation of genetically determined higher level of alanine and was statistically significant (95% confidence interval (CI) (0.80-0.99). The odds of CAD was 1.09 higher per one standard deviation of genetically determined higher level of glutamine and was not statistically significant (95% confidence interval (CI) (0.99-1.19). The odds of CAD was 0.94 lower per one standard deviation of genetically determined higher level of glycine and was statistically significant (95% confidence interval (CI) (0.91-0.98). After sensitivity analyses suggested pleiotropic effects, the analysis was repeated, removing SNPs with known pleiotropy. Results remained the same for all three amino acids. MI was not statistically significantly associated with any of the amino acids. This study provides genetic validation that alanine could be a new target of intervention to prevent the leading cause of global morbidity and mortality. Glutamine should be investigated further to determine its status as a risk factor for CAD. Glycine may decrease the risk of coronary artery disease however additional research is needed.

Recommended Citation

Uribe, Allan, "A MENDELIAN RANDOMIZATION STUDY OF CORONARY ARTERY DISEASE AND THREE AMINO ACIDS: ALANINE, GLYCINE, AND GLUTAMINE" (2019). CUNY Academic Works.
https://academicworks.cuny.edu/sph_etds/31